The purpose of this project is to obtain a more fundamental understanding of the consequences of biochemical and cellular responses by phagocytizing leukocytes to their endogenous generation and release of reductive products of oxygen. In our previous studies, we have shown that phagocytic function can be modified by these reductive products which include unstable free radicals as well as the more stable hydrogen peroxide. It would appear that two target sites within the phagocytic cell are the plasma membrane and the associated microfilament system that lies beneath it and the microtubular skeleton within the cytoplasm that reversibly polymerizes to control cell movement, degranulation, and restricts lateral movement of important surface proteins within the membrane. We hope to firmly document the precise phagocytic function that is altered by these free radicals and to attempt to modify this destruction by treatment of the host or the cells with antioxidant agents, for example, alpha-tocopherol for membrane associated structure and function and glutathione and other sulfhydryl amino acids for protection of the microtubular system within the cytoplasm of the cell. We also will study the purified components from other tissues with similar proteins such as bovine brain tubulin and actin, myosin, and actin-binding proteins from rabbit granulocytes. We will test artificial systems to generate free radicals upon the structure and function of these isolated proteins, in an attempt to relate our functional alterations to them. We will continue our search for disease states that are associated with alterations in these structures and functions. We will further explore animal models in the rat Vitamin E deficiency and selenium deficient glutathione peroxidase deficiency to study these important interrelationships. BIBLIOGRAPHIC REFERENCES: Baehner, R.L., Boxer, L.A., Allen, J.M., Davis, J.: Auto-oxidation as a basis for altered function by polymorphonuclear leukocytes. Blood 50: 1977. Baehner, R.L., Rister, M.: Effect of hyperoxia on superoxide anion and hydrogen peroxide production of polymorphonuclear leukocytes and alveolar macrophages. British Journal of Haematology 36: 245, 1977.